Scavenger Receptor A Dampens Induction of Inflammation in Response to the Fungal PathogenPneumocystis carinii

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Abstract
Alveolar macrophages are the effector cells largely responsible for clearance ofPneumocystis cariniifrom the lungs. Binding of organisms to β-glucan and mannose receptors has been shown to stimulate phagocytosis of the organisms. To further define the mechanisms used by alveolar macrophages for clearance ofP. carinii, mice deficient in the expression of scavenger receptor A (SRA) were infected withP. carinii, and clearance of organisms was monitored over time. SRA-deficient (SRAKO) mice consistently clearedP. cariniifaster than did wild-type control mice. Expedited clearance corresponded to elevated numbers of activated CD4+T cells in the alveolar spaces of SRAKO mice compared to wild-type mice. Alveolar macrophages from SRAKO mice had increased expression of CD11b on their surfaces, consistent with an activated phenotype. However, they were not more phagocytic than macrophages expressing SRA, as measured by an in vivo phagocytosis assay. SRAKO alveolar macrophages produced significantly more tumor necrosis factor alpha (TNF-α) than wild-type macrophages when stimulated with lipopolysaccharide in vitro but less TNF-α in response toP. cariniiin vitro. However, upon in vivo stimulation, SRAKO mice produced significantly more TNF-α, interleukin 12 (IL-12), and IL-18 in response toP. cariniiinfection than did wild-type mice. Together, these data indicate that SRA controls inflammatory cytokines produced by alveolar macrophages in the context ofP. cariniiinfection.